Klazen 2010

Methods	Design: multicentre (6 centres), two‐arm open‐label randomised controlled trial; control group allowed to cross‐over to vertebroplasty at one week post intervention Setting: the Netherlands and Belgium Timing: not reported Interventions: percutaneous vertebroplasty or usual care Sample size:a priori sample size calculation based on ability to detect a difference of 25% in significant pain relief with vertebroplasty compared with usual care based on a two‐sided type 1 error rate of 5% and power 80%. Analysis: intention‐to‐treat analysis
Participants	Number of participants 934 participants screened 732 were excluded (226 did not meet inclusion criteria, 229 met inclusion initially but then a decrease in pain during screening rendering them ineligible, 232 declined participation and 45 requested vertebroplasty) 202 patients were randomised (101 in percutaneous vertebroplasty, and 101 in conservative treatment) Data were available for 188 (96 (95%) for vertebroplasty and 92 (91%) for usual care) at the 1‐month follow‐up Data were available for 163 (86 (85%) for vertebroplasty and 77 (76%) for usual care) at the final 1‐year follow‐up Inclusion criteria Acute back pain for 6 weeks or less Pain on 0‐10 VAS of 5 or more Focal tenderness at fracture level, as assessed by an internist on physical examination Vertebral compression fracture on spine radiograph (minimum 15% height loss) at T5 or lower Bone oedema of vertebral fracture on MRI Decreased bone density (T scores ≤ 1) Exclusion criteria Severe cardio‐pulmonary comorbidity Untreatable coagulopathy Systemic or local spine infection Suspected underlying malignant disease Radicular syndrome Spinal‐cord compression syndrome Contraindication for MRI Baseline characteristics Vertebroplasty Group: Mean (SD) age: 75.2 (9.8) years; 70 female, 31 male Mean (SD) duration of back pain: 29.3 (17.1) days Number of VCFs at baseline: 2.4 (1.9) Mean (SD) pain at baseline: 7.8 (1.5) Mean (SD) RMDQ: 18.6 (3.6) Mean (SD) QUALEFFO: 58.7 (13.5) Bone density T score: ‐3.0 (1.17) Usual care group Mean (SD) age: 75.4 (8.4) years; 70 female, 31 male Mean (SD) duration of back pain: 26.8 (16.0) days Number of VCFs at baseline: 2.1 (1.5) Mean (SD) pain at baseline: 7.5 (1.6) Mean (SD) RMDQ: 17.2 (4.2) Mean (SD) QUALEFFO: 54.7 (14.4) Bone density T score: ‐3.0 (1.05)
Interventions	Percutaneous vertebroplasty Percutaneous vertebroplasty was performed using a single or biplane angiography system under fluoroscopic guidance. After local analgesia, two 11‐ or 13‐gauge bone‐biopsy needles were placed transpedicularly in the fractured vertebral body. Polymethylmetacrylate bone cement (Osteo‐Firm, COOK Medical, Bloomington, IN, USA) was injected through bone‐biopsy needles under continuous fluoroscopic monitoring to identify local cement leakage or migration into the venous system towards the lung. In patients who had more than one fracture with bone oedema on MRI, all vertebral bodies were treated in one or more procedures. After the procedure, a CT scan of the treated vertebral bodies was performed with 2 mm slices to identify cement leakage or other possible local complications. Usual care 'Optimal Pain Management (OPM)' consisted of the use of analgesics in ascending order Acetaminophen Tramadol Tramadol and acetaminophen Morphine Non‐steroidal anti‐inflammatory drugs (NSAIDs) for those already using or intolerant to opiate‐derivatives Corrections in dose and classification of pain medication were made when necessary by the internist, and in most cases physiotherapy was prescribed. Follow‐up care All patients received osteoporosis medication, such as bisphosphonates together with supplemental calcium and vitamin D.
Outcomes	Outcomes were reported at baseline, 1 week, and 1, 3, 6 and 12 months. Pain diary ‐ pain VAS and use of analgesia recorded daily to 1 month. Primary outcome Mean pain on VAS ranging from 0 (no pain) to 10 (worst pain ever); clinically significant pain relief was defined as a decrease of 3 points or more in VAS score from baseline Secondary outcomes Pain‐free days were defined as days with a VAS score of 3 or lower Cost‐effectiveness as costs per QALYs at one month and one year Quality of life measured with the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO)(scores range from 0 to 100, with lower scores indicating a better quality of life) Physical function: Roland‐Morris Disability Questionnaire (RMDQ) (modified 23‐item version, scores range from 0 to 23, with higher scores indicating worse physical functioning) Quality of life: European Quality of Life‐5 Dimensions (EQ‐5D) scale, with a score range of 0 to 1 (1 is best quality of life) Use of analgesia Incident radiographic vertebral fractures measured at 1, 3 and 12 months Adverse events Outcomes included in this review Mean pain (0 to 10 VAS; 0 is no pain) Function RMDQ (0 to 23 scale; 0 is better function) Quality of life measured with the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO, 0 to 100; 0 is better) Quality of life (EQ‐5D, scores range from 0 to 1, with 1 being best quality of life) Proportion with incident radiographic vertebral fractures
Source of funding	The study was sponsored by ZonMw (Dutch organisation for health care research and innovation of care), project number 945‐06‐351 and an unrestricted grant from the COOK Medical (Bloomington, IN, USA).
Notes	Trial registered at ClinicalTrials.gov. Registration number NCT00232466. "VERTOS II" Pre‐treatment group differences: participants allocated to vertebroplasty had worse scores for EQ5‐D; QUALEFFO and RMDQ at baseline. RMDQ and QUALEFFO means only shown graphically in the trial report. Dr Klazen provided mean (SD) data for the RMDQ, EQ5D and QUALEFFO at all time points to 12 months.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation codes with a block size of six.
Allocation concealment (selection bias)	Low risk	As an independent telephone operator allocated participants by telephone, the allocation was likely concealed from the investigators.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants and study personnel were aware of treatment assignment.
Blinding of outcome assessment (detection bias) Self‐reported outcomes (e.g., pain, disability)	High risk	Participants were not blinded to treatment assignment.
Blinding of outcome assessment (detection bias) Objective outcomes (e.g., radiographic outcomes)	High risk	Radiologists were not blinded to treatment assignment.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	A greater number of participants completed one‐year follow‐up in the vertebroplasty group (86/101, 85%) compared with 77/101 (76%) in the usual care group. Fifteen (15%) participants in the usual care group received vertebroplasty.
Selective reporting (reporting bias)	Low risk	The trial authors published the planned outcomes in a trial protocol and provided results for each planned outcome.
Other bias	High risk	Quality of life and disability were worse at baseline in the vertebroplasty group which may have biased the results favouring the vertebroplasty group.